Antibody and complement appear to mediate opposing effects with regard to interaction between mouse leukemia cells and the host immune response: Escape of tumor cells from immune destruction in the presence of antibody to certain tumor cell surface antigens (antigenic modulation) and rapid lysis of spontaneous leukemias following infusion of heparinized normal homologous or heterologous plasma (plasma therapy of leukemia). Analysis of the thymus-leukemia (TL) antigen system on leukemia cells indicates that TL antibody-induced modulation actually represents a blocking of guinea pig complement-mediated cytolysis, effected by formation of TL antigen-antibody aggregates within the cell surface membrane, intercalated by mouse C3 which prevents (sterically hinders) initiation of the lytic complement system. The mechanism is precisely the same in vitro and in vivo. Modulation does not occur in the absence of mouse C3 deposition on the cell surface, and is induced by IgG antibody but not IgM antibody. There is a precise coorelation between the capacity for an antigen to modulate and for leukemia cells bearing that antigen to escape destruction in immunocompetent hosts, although in the absence of mouse C3 deposition or in the presence of IgM antibody, tumor escape occurs although modulation is not achieved. These results suggest that a peculiar mobility of modulating antigens within the cell surface, innate or perhaps induced by antibody binding, is the driving force permitting tumor escape or modulation. Efforts to duplicate in vitro the effect of heparinized normal plasma in lysing mouse leukemia cells in situ have focussed on cell-mediate cytotoxicity and antibody- and complement-dependent cellular cytotoxicity. To date, no specific lysis in vitro has been obtained.